Rationale. Intracranial atherosclerotic disease (ICAD) is a known cause of stroke in about 80,000 patients every year in US. In addition it is suspected to be associated with cognitive impairment and dementia. However, despite being such a common health problem, the prevalence of this disease is unclear. Also, the degree of association of ICAD with cognitive impairment and dementia remains unstudied. We plan to study the prevalence of ICAD in US elderly population and also determine its association with cognitive impairment and dementia. Aims: The broad objective of our proposed project is to conduct an ancillary study in the subsample of 2000 subjects who are undergoing MRI in ARIC-NCS. Aims are 1) to estimate the prevalence of ICAD in the ARIC participant aged 70-89 years and 2) to determine whether ICAD is associated with dementia or mild cognitive impairment. Design/Methods: Atherosclerosis Risk in Communities is an NHBLI funded cardiovascular cohort that has followed about 16,000 subjects, aged 45-64 for last 25 years. Now, ARIC Neurocognitive Study (ARIC-NCS), funded by NHLBI, will perform magnetic resonance imaging (MRI) in 2000 of the remaining 7000 subjects. Neurocognitive testing will be performed as part of ARIC-NCS and the sample of 2000 subjects selected for MRI will include subjects with dementia (n=358), mild cognitive impairment (MCI) (n=761), and normal participants (n=878). We plan to acquire magnetic resonance angiography (MRA) studies on these 2000 subjects at the same time MRI images are being acquired for ARIC-NCS. We will measure luminal stenosis, a standard clinical parameter for ICAS, using MRA. In addition, we will measure intracranial vessel wall thickness, using a novel high-resolution MRI sequence. Vessel wall thickness may detect atherosclerotic changes without any significant stenosis and may be a better measure of atherosclerotic disease burden. In addition, compared to luminal stenosis, vessel wall thickness may also be more strongly associated with cognitive impairment or dementia. We will use two different definitions of ICAD to determine prevalence 1. luminal narrowing of >50%, and 2. vessel wall thickness of >0.6-mm. Implications. The study is based on new data that suggests asymptomatic ICAD is associated with cognitive impairment among elderly persons in the general population. Furthermore, asymptomatic ICAD may be associated with cognitive impairment in the absence of cerebral infarctions on MRI due to chronic hypoperfusion in the elderly population. This will also be the first study to determine the prevalence of asymptomatic ICAD in the US elderly population and its impact upon cognitive impairment. PUBLIC HEALTH RELEVANCE: Understanding the prevalence of intracranial atherosclerosis will help us study the primary prevention of stroke. If intracranial atherosclerosis is identified to be associated with cognitive impairment and dementia, it will offer promise toward search of preventive and therapeutic treatments of these common and major health issues.